Identifying the cell of origin and elucidating the mechanism of carcinogenesis and differentiation, in cervical cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16853
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Kawata Akira 東京大学, 医学部附属病院, 届出研究員 (90897290)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 子宮頸癌 / 起源細胞 / 扁平円柱上皮境界 / オルガノイド培養 / 混合癌 / 幹細胞 / HPV18型

Outline of Final Research Achievements

In genomic and transcriptomic analyses of HPV18-positive cervical cancers with mixed histological types, we revealed that the different histological types had a common cell of origin and that HPV integration could occur before differentiation into each histological type. In the analysis on human-derived SCJ organoids which reflect the environment of SCJ regions, we initially established a lentiviral vector which enables real-time monitoring of HPV18 early promoter activity, and then transduced it to SCJ organoids. In the promoter activated cells, significantly upregulated genes were identified. Among these genes, validation experiment using NIKS cell line suggested that NPM3, one of histone chaperone proteins may be involved in the maintenance of undifferentiated status.

Free Research Field

婦人科腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では、子宮頸癌の起源細胞についての新たな知見を示し、またHPV18型感染の標的細胞とウイルス複製の特徴を解明した。本研究で実施した、子宮頸部 SCJ オルガノイドに対して遺伝子導入を行う手法はこれまでに報告がなく、さらに我々が樹立したHPV18 型初期プロモーター活性を測定可能にするベクターシステムも革新的であり、いずれも今後のHPV感染症研究への幅広い応用が可能である。子宮頸癌において、特にHPV18型は早期診断が困難な病態や治療抵抗性を示す病態とも関連があり、本研究で得られた知見や手法は将来的な子宮頸癌治療や予防・診断について研究していく上での基礎となる重要なものである。